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Glutathione and glutathione S-transferase in benign and malignant prostate cell lines and prostate tissues
A T Canada1, K M Roberson, R L Vessella
1Department of Anesthesiology, Duke University Medical Center, Durham, NC, USA.
Abstract:
Metastatic prostate adenocarcinoma is unresponsive to alkylator chemotherapy with virtually no prolonged remissions. Glutathione (GSH) and glutathione S-transferase (GST) have been reported to play a role in tumor resistance to alkylator therapy; however, there are no baseline studies that have investigated and compared GSH and GST in human prostate cell lines and tissues. Thus, we determined the GSH content and GST activity in benign prostate, in primary and metastatic prostate adenocarcinoma tissues, in immortal adenocarcinoma cell lines, and in primary cell cultures derived from both benign prostate and primary prostatic carcinoma tissue. The GSH content was higher in the immortal cell lines than in the fresh tissues and primary cultures. Conversely, the GST activity was significantly higher in the tissues and primary cultures than in the cell lines. The GSH content and GST activity of the primary cultured prostatic cells were similar to those of the prostate tissues. The differences between the immortal prostate cancer cell lines and prostate tissue are of sufficient magnitude to suggest that in vitro results with cell lines may not extrapolate to prostate cancer in vivo. The GSH content and GST activity in a prostate specific antigen-secreting human prostate tumor xenograft, LuCaP23, maintained in nude mice were similar to those of human prostate tissue and primary cultures. Both the xenograft and primary cultures from patients with prostate cancer may be more appropriate models than established cell lines for investigating techniques to increase the effectiveness of alkylators in prostate cancer.
Insights
Glutathione (GSH) and glutathione S-transferase (GST) levels differ between prostate cancer cell lines and tissues. These differences suggest established cell lines may not accurately model in vivo prostate cancer, impacting alkylator chemotherapy research.
Area of Science:
- Oncology
- Biochemistry
- Pharmacology
Background:
- Metastatic prostate adenocarcinoma shows poor response to alkylator chemotherapy.
- Glutathione (GSH) and glutathione S-transferase (GST) are implicated in tumor resistance.
- Limited studies compare GSH and GST in prostate cancer cell lines versus tissues.
Purpose of the Study:
- To determine and compare GSH content and GST activity in various prostate cancer models.
- To assess the relevance of established cell lines for in vivo prostate cancer research.
- To identify appropriate models for improving alkylator chemotherapy efficacy.
Main Methods:
- Quantified GSH content and GST activity in benign prostate tissues, primary and metastatic prostate adenocarcinoma tissues, immortal cell lines, and primary cell cultures.
- Utilized a human prostate tumor xenograft (LuCaP23) in nude mice for comparison.
- Compared in vitro cell line data with in vivo tissue and xenograft data.
Main Results:
- Immortal cell lines exhibited higher GSH content but lower GST activity compared to fresh tissues and primary cultures.
- Prostate tissues and primary cultures showed similar GSH content and GST activity.
- Xenograft models demonstrated GSH and GST levels comparable to human prostate tissues.
Conclusions:
- Significant biochemical differences exist between established prostate cancer cell lines and actual tumor tissues.
- In vitro findings from established cell lines may not accurately predict in vivo responses to alkylator chemotherapy.
- Prostate tissue, primary cultures, and xenografts are more suitable models for studying alkylator resistance and developing new therapeutic strategies.